Pharmaceutical Research

, Volume 32, Issue 1, pp 222–237 | Cite as

Screening Methodologies for the Development of Spray-Dried Amorphous Solid Dispersions

  • Íris Duarte
  • José Luís Santos
  • João F. Pinto
  • Márcio Temtem
Research Paper

ABSTRACT

Purpose

To present a new screening methodology intended to be used in the early development of spray-dried amorphous solid dispersions.

Methods

A model that combines thermodynamic, kinetic and manufacturing considerations was implemented to obtain estimates of the miscibility and phase behavior of different itraconazole-based solid dispersions. Additionally, a small-scale solvent casting protocol was developed to enable a fast assessment on the amorphous stability of the different drug-polymer systems. Then, solid dispersions at predefined drug loads were produced in a lab-scale spray dryer for powder characterization and comparison of the results generated by the model and solvent cast samples.

Results

The results obtained with the model enabled the ranking of the polymers from a miscibility standpoint. Such ranking was consistent with the experimental data obtained by solvent casting and spray drying. Moreover, the range of optimal drug load determined by the model was as well consistent with the experimental results.

Conclusions

The screening methodology presented in this work showed that a set of amorphous formulation candidates can be assessed in a computer model, enabling not only the determination of the most suitable polymers, but also of the optimal drug load range to be tested in laboratory experiments. The set of formulation candidates can then be further fine-tuned with solvent casting experiments using a small amount of API, which will then provide the decision for the final candidate formulations to be assessed in spray drying experiments.

Key Words

Amorphous solid dispersion miscibility screening method solvent casting spray drying 

ABBREVIATIONS

ASD(s)

Amorphous solid dispersion(s)

SDD(s)

Spray dried dispersion(s)

ITZ

Itraconazole

SC

Solvent casting

SD

Spray drying

HPMCAS-MG

Hydroxypropyl methylcellulose acetate succinate (grade MG)

PVP/VA 64

Polyvinylpyrrolidone-vinyl acetate copolymer

Eudragit® EPO

Copolymer of dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate

Tg

Glass transition temperature

Supplementary material

11095_2014_1457_MOESM1_ESM.docx (6 mb)
ESM 1(5.99 mb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Íris Duarte
    • 1
    • 2
  • José Luís Santos
    • 2
  • João F. Pinto
    • 1
  • Márcio Temtem
    • 2
  1. 1.iMed – Research Institute for Medicines and Pharmaceutical SciencesUniversity of Lisbon, Faculty of PharmacyLisboaPortugal
  2. 2.R&D Drug Product DevelopmentHovione Farmaciência SALouresPortugal

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